1 human genetics concepts and applications tenth edition ricki lewis copyright ©the mcgraw-hill...
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Human GeneticsConcepts and Applications
Tenth Edition
RICKI LEWIS
Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display
PowerPoint® Lecture Outlines Prepared by Johnny El-Rady, University of South Florida
10Gene Action:From DNA to Protein
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Gene Expression
The human genome contains about 20,325 protein-encoding genes
- However, this represents only a small part of the genome
Much of the human genome controls protein synthesis
- Including the time, speed, and location
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Proteins have diverse functions in the body
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Gene Expression
Production of protein from instructions on the DNA
Gene expression requires several steps
- Transcription = Production of mRNA
- Translation = Production of protein using mRNA, tRNA, and rRNA
- Folding of the protein into the active 3-D form
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5Figure 10.1
Central Dogma
Figure 10.1
The directional flow of genetic information
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Transcription
RNA is the bridge between DNA and protein
RNA is synthesized from one strand of the DNA double helix, which is called the template strand
The complementary strand is called the coding strand of DNA
Requires the enzyme RNA polymerase
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Figure 10.2
Transcription
Figure 10.2
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Nucleic Acids
There are two types of nucleic acids
- RNA
- DNA
Both consist of sequences of N-containing bases joined by sugar-phosphate backbones
- However, they differ in several aspects
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Table 10.2
Nucleic Acids
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Table 10.2
Figure 10.3
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Types of RNA
There are three major types of RNA
- messenger RNA or mRNA
- ribosomal RNA or rRNA
- transfer RNA or tRNA
Other classes of RNA control gene expression
- Will be discussed in Chapter 11
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Major Types of RNA
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mRNA
Carries information that specifies a particular protein
Produced in the nucleus
Transported to the ribosome
A three nucleotide codon specifies a particular amino acid
Most mRNAs are 500-4,500 bases long
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rRNA
Associate with proteins to make up ribosomes
Ribosomes consist of two subunits that join during protein synthesis
rRNAs provide structural support
- Some are a catalyst (ribozymes)
Most rRNAs are from 100-3,000 bases long
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rRNA
Figure 10.4
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tRNA
Only 75-80 bases long
The 2-D shape is a cloverleaf shape
The 3-D shape is an inverted L
Has two business ends:
- The anticodon forms hydrogen bonds with the mRNA codon
- The 3’ end binds the amino acid specified by the mRNA codon
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Figure 10.5
Figure 10.6
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Transcription Factors
In bacteria, operons control gene expression
In more complex organisms transcription factors control gene expression and link genome to environment
- These contain DNA-binding domains
About 2,000 in humans
Mutations in transcription factors may cause a wide range of effects
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Steps of Transcription
Transcription is described in three steps:
- Initiation
- Elongation
- Termination
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Steps of Transcription
In transcription initiation, a cascade of transcription factors bind to the promoter region of a gene
These open a pocket allowing the RNA polymerase to bind just in front of the start of the gene sequence
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Figure 10.7
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Steps of Transcription
During elongation, RNA polymerase reads the nucleotides on the template strand from 3’ to 5’ and creates an RNA molecule that looks like the coding strand
Then termination occurs when sequences in the DNA prompt the RNA polymerase to fall off ending the transcript
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Figure 10.8
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24Figure 2.3
Transcription Animation
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Simultaneous Transcription of mRNAs
Several mRNAs may be transcribed from the same template DNA strand at a time
Figure 10.9
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RNA Processing
In eukaryotes, mRNA transcripts are modified before they leave the nucleus
Several steps process pre-mRNA into mature mRNA
1) A methylated cap is added to the 5’ end
- Recognition site for protein synthesis
2) A poly-A tail is added to the 3’ end
- Stabilizes the mRNA
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3) Splicing occurs
- Introns (“intervening sequences”) are removed
- Exons (“expressed sequences”) are spliced together
- Note that introns may outnumber and outsize exons
Finally, the mature mRNA is sent out of the nucleus
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28Figure 10.10
Figure 10.10
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Translation
The process of reading the mRNA base sequence and creating the amino acid sequence of a protein
Occurs on the ribosome
Figure 10.11
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The Genetic Code
The correspondence between the chemical languages of mRNA and proteins
In the1960s, researchers used logic and clever experiments with synthetic RNAs to decipher the genetic code
More recently, annotations of the human genome has confirmed and extended the earlier work
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The Genetic Code
It is a triplet code
- Three successive mRNA bases form a codon
There are 64 codons, including:
- One start signal (AUG)
- Three stop signals (UAA, UAG, and UGA)
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Figure 10.12
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The Genetic Code
It is non-overlapping
It is degenerate
- Two or more codons may specify the same amino acid (synonymous codons)
It is universal
- Evidence that all life evolved from a common ancestor
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34Figure 10.13
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Reading Frame
A sequence of amino acids encoded from a certain starting point in a DNA/RNA sequence
Figure 10.14
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36Table 10.4
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Translation
Requires mRNA, tRNAs with amino acids, ribosomes, energy molecules (ATP, GTP) and protein factors
Divided into three steps:
- Initiation
- Elongation
- Termination
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Translation Initiation
The leader sequence of the mRNA forms H-bonds with the small ribosomal subunit
The start codon (AUG) attracts an initiator tRNA that carries methionine
This completes the initiation complex
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Figure 10.15
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Translation Elongation
The large ribosomal subunit joins A second tRNA binds to the next mRNA codonFirst peptide bond forms between the two amino
acids- Catalyzed by an rRNA ribozyme
tRNAs bring in more amino acids, as the ribosome moves down the mRNA- The P site bears the polypeptide chain- The A site holds the newest tRNA
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Figure 10.16
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Translation Termination
Occurs when a stop codon enters the A site of the ribosome
A protein release factor frees the polypeptide
The ribosomal subunits separate and are recycled
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Figure 10.17
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44Figure 2.3
Translation Animation
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Multiple Copies of a Protein Can be Made Simultaneously
The closer to the end of the gene, the longer the polypeptide
Figure 10.18
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Protein Structure
Proteins fold into one or more 3-D shapes or conformations
There are four levels for protein structure
- Primary (1O) structure
- Secondary (2O) structure
- Tertiary (3O) structure
- Quaternary (4O) structure
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Figure 10.19
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Protein Folding
Protein folding begins as translation proceeds
Enzymes and chaperone proteins assist
Should a protein misfold, an “unfolded protein response” occurs
- Protein synthesis slows or even stops
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Protein Misfolding
Misfolded proteins are tagged with ubiquitin
Then, they are escorted to a proteasome, a tunnel-like multiprotein structure
As the protein moves through the tunnel, it is straightened and dismantled
Proteasomes also destroy properly-folded proteins that are in excess or no longer needed
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Protein Misfolding
Figure 10.20
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Protein Misfolding
Most misfolded proteins are the result of errors in one of the steps of protein synthesis and processing
In several disorders that affect the brain, the misfolded proteins aggregate - The protein masses that form clog the proteasomes and inhibit their function
Different proteins are affected in different disorders
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Protein Misfolding
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Phenylketonuria (PKU)
Defect is in the enzyme phenylalanine hydroxylase which normally breaks down phenylalanine
The mutation is inherited from carrier parents
A localized misfolding occurs
- Misfolding spreads until the entire four-subunit enzyme can no longer function
The buildup of phenylalanine causes mental retardation
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Figure 10.21
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Prions
Prion protein (PrP) can fold into any of several conformations
One conformation is aberrant
- Moreover, it can be passed on to other prions upon contact, propagating like an “infectious” agent
In addition, the aberrant conformation can form even in the wild-type protein
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Prions
Figure 10.22
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Prion DiseasesPrion diseases are called transmissible
spongiform encephalopathies (TSEs)
- They have been found in 85 species
Examples: Scrapie (sheep); Kuru (humans); Bovine spongiform encephalopathy (cows)
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59Figure 2.3
Prion Animation
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